Nanomaterials based on metal oxides (MexOy) are employed as catalysts and/or sorbents in processes undergoing conditions in supercritical water (scH2O), the “green” reaction medium used to obtain energy relevant products. Their properties are greatly affected by the synthesis method used to produce the active MexOy. Moreover, in order to maintain their performance, it is more practical and cost-effective to use supported MexOy nanoparticles. Within this context, the present work deals with the preparation of carbon-supported ZnO and CuO composites by an innovative method based on impregnation under scH2O conditions. Metal oxides were impregnated on a carbon (C) support using a continuous flow tubular reactor. The results show that impregnation in scH2O is a promising approach for the preparation of ZnO/C and CuO/C composite materials. This one-step synthesis method, in a continuous flow, uses neither seed layer nor mineralizer, and it needs substantially lower preparation times than the conventional impregnation methods.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary & safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

The concept of “hyperferritinemic syndrome” defines a complex pathophysiological and clinical entity, characterized by a systemic hyperinflammatory state, generally associated with elevated levels of proinflammatory cytokines (hypercytokinemia) and high serum levels of ferritin (hyperferritinemia), traditionally recognized as an iron-binding plasma protein involved in the storage of iron in a biologically available form for different physiological cellular processes. Recent studies have shown that ferritin has other important functions as well, operating both as a proinflammatory mediator and as a immunosupressive agent, its elevated levels in the serum being detected in various conditions associated with inflammatory states, such as infectious diseases, autoimmune and autoinflammatory disorders and, in some cases, in malignancies. Catastrophic antiphospholipid syndrome (cAPS), systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD) and acquired forms of hemophagocytic lymphohistiocytosis (HLH), which includes macrophage activation syndrome (MAS), have been associated with hyperinflammatory states and dramatic elevations of serum ferritin, generating hyperferritinemic syndromes. Severe forms of coronavirus disease-2019 (COVID-19), in which MAS may frequently develop, has also been linked to the development of a hyperferritinemic syndrome. This review offers several insights into the physiological and pathophysiological roles of ferritin in several (hyper-)inflammatory diseases, but also into the causal entities, the underlying pathophysiological mechanisms, clinical manifestations and diagnostic features of somewhat obscure, yet potentially fatal pathological conditions, reunited under the concept of hyperferritinemic syndromes.

Automatic ship detection provides an essential function towards maritime domain awareness for security or economic monitoring purposes. This work presents an approach for training a deep learning ship detector in Sentinel-2 multispectral images with few labeled examples. We design a network architecture for detecting ships with a backbone that can be pre-trained separately. By using Self Supervised Learning, an emerging unsupervised training procedure, we learn good features on Sentinel-2 images, without requiring labeling, to initialize our network’s backbone. The full network is then fine-tuned to learn to detect ships in challenging settings. We evaluated this approach versus pre-training on ImageNet and versus a classical image processing pipeline. We examined the impact of variations in the self-supervised learning step and we show that in the few-shot learning setting self-supervised pre-training achieves better results than ImageNet pre-training. When enough training data is available, our self-supervised approach is as good as ImageNet pre-training. We conclude that a better design of the self-supervised task and bigger non-annotated dataset sizes can lead to surpassing ImageNet pre-training performance without any annotation costs.

The Active Distribution Networks (ADNs) are Multi-Input Multi-Output (MIMO) systems with coupled dynamics which cause interactions among the control loops of the Distributed Energy Resources (DERs). This undesired effect lead to performance degradation in the voltage control. To mitigate the effects of these unavoidable coupling, the present paper proposes a systematic design procedure based on the analysis of the interaction's sources. In details, each DER is equipped with a double loop PI to control the active and reactive powers output by the Voltage Source Converter (VSC) which connects the DER to the network's node. Furthermore, to guarantee Ancillary Services (ASs), the two loops are coupled by a simple mechanism of cooperation of the active power to voltage regulation realized by a filtered droop law. To achieve voltage regulation with reduced loop interactions, the PI parameters and the filter's pulse are designed according to a two sequential steps procedure based on the (Internal Model Control) IMC technique. Simulation studies are finally presented to demonstrate that the proposed design method achieves both reduction of the loop interaction and robust voltage control in presence of model parameter uncertainty in the MIMO model.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

The Sentinel-2 satellite mission offers high resolution multispectral time series image data, enabling the production of detailed land cover maps globally. At this scale, the trade-off between processing time and result quality is a central design decision. Currently, this machine learning task is usually performed using pixelwise classification methods. The radical shift of the computer vision field away from hand engineered image features and towards more automation by representation learning comes with many promises, including higher quality results and less engineering effort. In this paper we assess fully convolutional neural networks architectures as replacements for a Random Forest classifier in an operational context for the production of high resolution land cover maps with Sentinel-2 time series at the country scale. Our contributions include a framework for working with Sentinel-2 L2A time series image data, an adaptation of the U-Net model for dealing with sparse annotation data while maintaining high resolution output, and an analysis of those results in the context of operational production of land cover maps.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

During an epidemic outbreak it is useful for planners and responsible authorities to be able to plan ahead to estimate when an outbreak of an epidemic is likely to ease and when the last case can be predicted in their area of responsibility. Theoretically this could be done for a point source epidemic using epidemic curve forecasting. The extensive data now coming out of China makes it possible to test if this can be done using MS Excel a standard spreadsheet program available to most offices. The available data is divided up for whole China and the different provinces. This and the high number of cases makes the analysis possible. Data for new confirmed infections for Hubei, Hubei outside Wuhan, China excluding Hubei as well as Zhejiang and Fujian provinces all follow a log-normal distribution that can be used to make a rough estimate for the date of the last new confirmed cases in respective areas. In the version 2 continuation work, 9 additional days were added for the Chinese data to evaluate the previous predictions. The extra data then available from China follows the previous predicted trend supporting the usefulness of this simple technique. In the version 2 we also tested the feasibility for a non-specialist to make similar predictions using additional data from S Korea now available. In this third continuation the predictions for Version 2 are evaluated for S Korea and fits well the beginning of the decline but it seems to be difficult to bring down numbers of cases per day under about 100 new cases per day, potential reasons for this is discussed. To further evaluate when in a prediction becomes reliable the Chinese data was used to evaluate to make predictions for each day around the peak in number of cases and after2-3 consecutive days of decreasing new cases per day the prediction becomes reliable. In version 3 data for Italy just reaching this point was used to make further predictions for that country. A second new analysis was also added to use the fitted equation to detect when the acceleration of new cases per day stopped increasing exponentially. In the Chinese case this measured point coincides with the date of the complete Hubei lockdown and in the new Italian analysis it coincides with the mandatory Italian lockdown. Predicted dates for the end of the Italian outbreak is also added. In version 4 we expand the analysis to selected European countries, USA and the World as a whole and try to predict the end of the outbreak. We further discuss the apparent success of the used techniques that might work to introduce a “new normal” not very different to the previous to stop secondary outbreaks of COVID19 and future COVIDs that are sure to come.

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

The Solvency II regulatory framework specifies procedures and parameters for determining solvency capital requirements (SCRs) for insurance companies. The proposed standard SCR calculations involve two steps. The Value–at–Risk (VaR) of each risk driver is measured and, in a second step, all components are aggregated to the company’s overall SCR, using the Standard Formula. This formula has two inputs: the VaRs of the individual risk drivers and their correlations. The appropriate calibration of these input parameters has been the purpose of various Quantitative Impact Studies that have been conducted during recent years. This paper demonstrates that the parameter calibration for the equity–risk module—overall, with about 25%, the most significant risk component—is seriously flawed, giving rise to spurious and highly erratic parameter values. As a consequence, an implementation of the Standard Formula with the currently proposed calibration settings for equity–risk is likely to produce inaccurate, biased and, over time, highly erratic capital requirements.

Nonequilibrium work switching simulations and Jarzynski’s equation are a reliable method to compute free energy differences, ΔAlow→high, between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly get very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment, such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute ΔAlow→high reliably. In this study, we investigate two approaches towards an affordable protocol, with emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges which resembles the charge distribution of the desired high level makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of partial charges used, the number of waters in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.

The objective of the analysis carried out in this paper is to quantify the impact of subsidies on the activity of two vegetable farms, of different sizes in terms of agricultural area under cultivation, 600 ha and 3000 ha, which can constitute a model at macroeconomic level, indicating the ways in which these farms can ensure their income. For the analysis carried out, indicators were taken into account concerning production, net profit and subsidies received over a period of three years for the agricultural crops grown on these farms, identifying their contribution and effects on profitability. Descriptive statistics, visual inspections and basic comparison methods were also used, thus determining the patterns of the impact of subsidies and their variation for each of the existing crops in the vegetable farms studied. The data on which the statistical models are based are extracted from the financial statements of the farms analysed, giving the possibility of a predictive extension of the evolution of income and, very importantly, of their profitability. The conclusions revealed, for the 600 ha vegetable farm, that this farm maintained its area constant during the analysis period, benefiting from annual subsidies, and that the practice of crop diversification (rape, barley, winter wheat, oats, soybean, maize, lucerne), appropriate rotation, conservation farming and crop irrigation on 85.34% of the area, ensured average yields/ha that exceeded those recorded at national and regional level, except for 2020. The economic performance of this farm is oscillating in the period 2018-2021, with the ability to consistently generate profit, but in 2020 it is close to break-even, a year in which subsidy income tipped the balance towards positive but modest financial results. For this farm, the statistical model carried out was inconclusive because the farm optimises its cropping plan every year, depending on agrometeorological predictions, subsidy levels and market trends, changing crops, thus not being able to estimate the extent to which each crop contributes to maintaining the financial balance of the farm. Thus, although subsidies have impacted the level of net income, the extent to which they have done so is unclear. For the 3000 ha farm, the findings revealed that this farm also has a roughly constant area in use over the analysis period and for which it receives subsidies. This farm practices crop diversification (rape, barley, winter wheat, sunflower, soybean, grain maize, late potatoes, sweet potato, carrot and flowers) and adequate crop rotation. The data highlight that subsidies played a significant and sometimes overwhelming role in determining the gross output of each crop to achieve a positive value of this indicator. Modern conservation farming technologies and crop irrigation on 74.14% of the area justify the average yields/ha achieved, which again exceeded those recorded at national, regional and county level, with the exception of 2020. Maize and soybean crops consistently contributed to the farm's income, with a high gross product and net income, despite changes in the average yield per hectare achieved each year. Good and rising economic performance for this farm during the period under review, which justifies the profitability of the business from an economic, financial and commercial point of view. Although there have been fluctuations in the value of yields realized on different crops, net revenues continued to be high and even up significantly in 2021. Thus, the study highlighted and identified trends and patterns in agriculture, patterns that can serve as a source of information for relevant policy decisions, playing a key role in guiding future research and allocating resources efficiently in the agricultural sector.

In the context of the COVID-19 pandemic, countries around the world varied in the strength and timeliness of their responses. In Romania, specific challenges were faced with regards to managing the spread and limiting the impact of the disease, ranging from healthcare infrastructure to demographic and sociocultural aspects. As the country has a sizeable diaspora, major difficulties were faced when large numbers of individuals from highly affected areas returned to Romania. However, the fast implementation of control measures successfully averted a surge in the number of COVID-19 cases. This delayed the overburdening of an already challenged healthcare system during the initial phases of the epidemic. Furthermore, early control was facilitated by the exploitation of communication channels that penetrated all layers of society, from ordinary citizens to governmental authorities and high-ranking religious figures. The management of the COVID-19 crisis in Romania illustrates the importance of a fast initial response which takes into account the role played by sociocultural aspects in the context of an epidemic. As the challenges faced by Romania are not unique, these results could inform future public health strategies worldwide.

The results of the investigation showed that second-order kinetics govern the adsorption process, and the corresponding rate constants were found. To evaluate the parameters related to the adsorption process, the adsorption equilibrium was examined using a variety of mathematical models, such as the Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich isotherm models. The Langmuir isotherm was found to be the best appropriate among all models for describing the adsorption of Cu2+ and Ni2+ ions using bio-nanocomposite beads. The positive values of ΔH° indicate that the adsorption is physical and endothermic, in agreement with experimental results. The negative value of ∆G° shows that the adsorption process is spontaneous. Positive ΔS° values indicate increased randomness at the solid/liquid interface, during adsorption of Cu2+ and Ni2+ cations onto the engineered bio-nanocomposite. The maximum adsorbed amounts of metal ions by the bio-nanocomposite used were 370.37 mg/g for Ni2+ and 454.54 mg/g for Cu2+ from single system. For the binary system, according to the Langmuir isotherm, the maximum adsorbed amounts of Ni2+ and Cu2+ were 357.14 mg/g and 370,37 mg/g, respectively. There is proof that Alginate-Moroccan clay bio-nanocomposites can serve as a different, less expensive source of sorbents for the removal of metal ions from single and binary systems.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

The UV/Vis absorption energies (νmax) of different solvatochromic probes measured in co-solvent/water mixtures are analysed as a function of the average molar concentration (Nav) of the solvent composition. Nav is discussed in terms of the underlying average molar mass (mol average or mass average) of the mixture. ET(30) of Reichardt`s dye B30 is the focus of the analysis. Methanol, ethanol, 1,2-ethanediol, 2-propanol, 2-methyl-2-propanol, 2-butoxyethanol, formamide, N-methylformamide (NMF), dimethylformamide (DMF), N-formylmorpholine (NFM), 1,4-dioxane and DMSO were used as co-solvents. Significant linear dependencies of ET(30) as a function of Nav can be demonstrated for formamide/water, 1,2-ethanediol/water, NMF/water and DMSO/water mixtures over the whole composition range. These mixtures belong to the group of solvents that do not enhance the water structure according to the Marcus classification. The specifics of the 1,4-dioxane/water mixtures are discussed. For alcohol/water mixtures with enhanced water structure, the influence of the solvent microstructure on ET(30) is particularly evident.

Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process. The benefits offered by the LIF experimental technique have been demonstrated and some frequent problems in its application analysed. The mixing time results for configurations with and without baffles for three types of impellers and four different rotational speeds have been presented. The false shorter mixing times in the non-baffled configurations have been observed and this phenomena explained by the existence of two segregated zones in the reactor and confirmed by additional experiments. The precise measurements in these cases have been shown as difficult using the LIF technique, particularly for higher rpms. The experimental data has been compared to the preliminary simulation results obtained from the Smoothed Particle Hydrodynamics method and the standard k-ε turbulence model with the modest success. The shortcomings of the SPH model have been recognized and the directions for the future work discussed.

Ovarian tissue cryopreservation (OTC) or testicular tissue cryopreservation (TTC) are effective and often the only options for fertility preservation in female or male patients due to oncological, medical, or social aspects. While TTC and resumption of spermatogenesis, either in vivo or in vitro, has still be considered an experimental approach in humans, OTC and autotransplantation has been applied increasingly to preserve fertility with more than 200 live births worldwide. However, the cryopreservation of reproductive cells followed by the resumption of gametogenesis, either in vivo or in vitro, may interfere with sensitive and highly regulated cellular processes. In particular, the epigenetic profile, which includes not just reversible modifications of the DNA itself but also post-translational histone modifications, small non-coding RNAs, gene expression and availability, and storage of related proteins or transcripts, have to be considered in this context. Due to complex reprogramming and maintenance mechanisms of the epigenome in germ cells, growing embryos, and offspring, OTC and TTC are carried out at very critical moments early in the life cycle. Given this background, the safety of OTC and TTC taking into account the epigenetic profile has to be clarified. Cryopreservation of mature germ cells (including Metaphase II oocytes and mature spermatozoa collected via ejaculation or more invasively after testicular biopsy) or embryos has been used successfully for many years in Medically Assisted Reproduction (MAR). However, tissue freezing followed by in vitro or in vivo gametogenesis has become more attractive in the past, while few human studies have analysed the epigenetic effects, with most data deriving from animal studies. In this review, we highlight the potential influence of the cryopreservation of immature germ cells and subsequent in vivo or in vitro growth and differentiation on the epigenetic profile in humans and animals.

Abstract: Rice is one of the most important food crops in sub-Saharan Africa. Climate change, variability, and economic globalization threaten to disrupt rice value chains across the subcontinent, undermining their important role in economic development, food security, and poverty reduction. This paper maps existing research on the vulnerability of rice value chains, synthesizes the evidence and the risks posed by climate change and economic globalization, and discusses agriculture and rural development policies and their relevance for the vulnerability of rice value chains in sub-Saharan Africa. Important avenues for future research are identified. These include the impacts of multiple, simultaneous pressures on rice value chains, the effects of climate change and variability on parts of the value chain other than production, and the forms and extent to which different development policies hinder or enhance the resilience of rice value chains in the face of climatic and other pressures.

Using geometric considerations, we provide a clear derivation of the integral representation for the error function, known as the Craig formula. We calculate the corresponding power series expansion and prove the convergence. The same geometric means finally help to systematically derive handy formulas that approximate the inverse error function. Our approach can be used for applications in e.g. high-speed Monte Carlo simulations where this function is used extensively.

Background. In the last decade, it was concluded that glaucomatous optic neuropathy is part of the neurodegenerative diseases in which destructive neuronal lesions are located not only in the structure of the retina, but they are also present at the level of the central visual and nervous pathways. Patients with Primitive Open Angle Glaucoma may have experienced changes such as sensorineural hearing loss as well as balance changes. The purpose of this study is to evaluate the degree of involvement of the auditory system in patients with glaucoma, the structural changes in the optic nerve and, to establish correlation between the hearing loss and structural changes in the optic nerve. The subjects included in the study are grouped as follows: a group of patients with glaucoma that will be compared to a group of patients without glaucoma only as well as identi-fy-ing the evolution of structural changes in optic nerve to patients with glaucoma and to normal patients. Material and methods. It is a prospective, cross-sectional study on 32 eyes of 16 subjects with Primitive Open Angle Glaucoma in a study group and 24 eyes of 12 healthy subjects in con-trol group with a mean age of 62 years in both groups. Both groups underwent ophthalmo-logical, audiological and radio imaging evaluation: Pure-tone audiometry (PTA) were recorded, oph-thalmologic evaluations according to a standardized protocol and MRI cerebral examination was performed. Results: In the Study group patients, compared to the Control group, the average lev-els of the left PTA, the cup/disc (C/D) area in both eyes, the C/D ratio in both eyes are in-creased. The mean level of Retinal nerve fiber layer (RNFL) mean thickness was slightly lower in patients with glaucoma. Multivariate analysis demonstrates that gender can be a good predictor of C/D area, gender and age can be good predictors of PTA both eyes and C/D ratio in the right eye, and gender, age and background can be good predictors of disc area in the left eye. Conclu-sions: Pa-tients with Primitive Open Angle Glaucoma show changes in audiometry test in correla-tion with ophthalmological parameters demonstrating that the auditory system can be affected in Primitive Open Angle Glaucoma. This study emphasizes the problem of interdisciplinarity in medicine with the aim of ensuring the quality of life of patients with glaucoma. A good collabora-tion between ophthalmologist and otolaryngologist will be very useful for these patients.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

We prove a quasi-pseudometric version of the strong Ekeland principle proved by P. Georgiev and T. Suzuki.

Precise and fast position tracking is essential for the correct operation of many industrial robots and CNC machine tools. This subject is also important in the control of the mount of the astronomical telescope, especially for the tracking of artificial satellites. As system parameters can change, a control method that is robust to changes in parameters must be used. Such a method is the sliding control, which, however, ensures the robustness only after reaching the sliding surface. Therefore, a new method was proposed in the paper, which eliminates the phase of reaching the sliding surface. The method consists of using a reference trajectory generator and determining the generalized error in relation to this trajectory. The procedure for designing the control system is presented. Next, the proposed method was verified on the laboratory stand. The described control method provides a robust system operation and can be easily implemented in the control system.

The conceptual reconstruction of Neiwan powerhouse is one of the key activities under the current ongoing mapping project of Taiwanese hydropower plants that mainly took place between 2013 and 2015 and is now focused on micro, pico, and historical power plants. Judging from the fact that the oldest hydropower plant in Taiwan named Guishan starts its operation in 1905, Neiwan powerhouse was among the very first powerhouses that were built across the island to support the electrification of Taiwan. However, the main function of the single turbine equipped Neiwan micro powerhouse was to support mainly the military needs and protect the territories occupied by Japanese troops. Since the powerhouse was built in 1909 and operates only something about 10 year there are very little physical materials or evidence along with contemporaries. Therefore the further reconstruction is based mainly on physical observation of the remains located at the site, old photographs, related articles, treatises and typology of mechanical and civil constructions of other hydropower plant cases in Taiwan hence this paper´s main intention is to pitch a concept reconstruction rather than definite conclusion.

The ability to identify and rank risk is essential for efficient and effective supervision of financial service firms, such as banks and insurers. Risk ranking ensures limited resources are allocated where they are most needed. Today, automatic risk identification within insurance supervision primarily relies on quantitative metrics based on numerical data (e.g. returns). The purpose of this work is to assess whether Natural Language Processing (NLP) and cognitive networks can achieve similar automated risk ranking and identification by analysing textual data, i.e. NIDT=829 investor transcripts from Bloomberg. To this aim, this work explores and tunes 3 NLP techniques: (1) keyword extraction enhanced by cognitive network analysis; (2) valence/sentiment analysis; and (3) topic modelling. Results highlight that keyword analysis, enriched by term frequency-inverse document frequency scores and semantic framing through cognitive networks, could detect events of relevance for the insurance system like cyber-attacks or the COVID-19 pandemic. Cognitive networks were found to highlight events that related to specific financial transitions: The semantic frame of "climate" grew in size by +538% between 2018 and 2020 and outlined an increased awareness that agents and insurers expressed towards climate change. A lexicon-based sentiment analysis achieved a Pearson’s correlation of ρ=0.16 (p<0.001,N=829) between sentiment levels and daily share prices. Although relatively weak, this finding indicates that insurance jargon is insightful to support risk supervision. Topic modelling is considered less amenable to support supervision, because of a lack of results’ stability and an intrinsic difficulty to interpret risk patterns. We discuss how these automatic methods could complement existing supervisory tools in automated risk ranking.

FinTech has been in the focus of the discussion for quite some time. However, the market share of FinTech companies is still relatively small in compared to more traditional financial services. The purpose of this paper is to analyse the status quo, current developments and challenges ahead for the Latvian FinTech sector. We combine three analyses: the political and legal, the economic, the social and the technological environment (PEST) analysis, an analysis of the size and performance of FinTech companies during the last 10 years, and a survey among FinTech companies. We find that the current status of regulation is one of the main obstacles to FinTech development, because it does not sufficiently consider FinTech-specific aspects. Problems in attracting skilled workforce, and an environment that is not very supportive of new developments in finance are further challenges and might explain at least part of the growth and performance difficulties. A revision, modernization and harmonization of regulation is essential to create a level playing field for all market participants: FinTech companies, traditional financial service providers and those originally traditional players that are integrating FinTech solutions in their business model. Further efforts are also required to foster the Latvia’s attractiveness for skilled workforce. We hope that this study helps increase the visibility of Latvian FinTech and contributes to the development of the new Latvian FinTech strategy.

Arthroplasty is commonly performed to treat advanced osteoarthritis or other degenerative joint conditions, but it can also be considered for young patients with severe joint damage that significantly limits their functionality and quality of life. Young patients are still at risk of aseptic mobilization and bone resorption due to the phenomenon of stress-shielding that causes an uneven distribution of tensions along the femoral contact surface prosthesis. This phenomenon can be limited by appropriately choosing the material of the prosthesis or by varying its stiffness, making sure that its mechanical behavior simulates that of the femur as much as possible. The aim of this study is to evaluate the mechanical behavior of a prosthesis optimized both in shape and material and in comparing the results with a standard titanium prosthesis. Methods: Through three-dimensional modeling and the use of software finite element method (FEM) such as ANSYS we simulate the mechanical behavior of traditional prosthesis and prosthesis optimized topologically respecting the ASTM F2996-13 standard Results: With topological optimization there is a stress reduction from 987 Mpa to 810 Mpa with a mass reduction of 30%. With the use of carbon fiber, it is possible to further reduce stress to 509 Mpa. Conclusions: The reduction of stress on the femoral stem allows an optimal distribution of the load on the cortical bone thus decreasing the problem of stress-shielding.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

The dynamic interplay of signaling networks in most major cellular processes is characterized by the orchestration of reversible protein phosphorylation. Consequently, analytic methods like quantitative phospho-peptidomics has been pushed forward from a highly specialized edge-technique to a powerful and versatile platform for comprehensively analyzing the phosphorylation profile of living organisms. Despite enormous progress in instrumentation and bioinformatics, a major problem remains a high number of missing values caused by the experimental procedure due to either a random phospho-peptide enrichment selectivity or borderline signal intensities, which both cause the exclusion for fragmentation using the commonly applied data dependent acquisition (DDA) mode. Consequently, an incomplete dataset reduces confidence in the subsequent statistical bioinformatic processing. Here, we successfully applied data independent acquisition (DIA) by using the filamentous fungus Magnaporthe oryzae as model organism and could prove that while maintaining data quality (such as phosphosite and peptide sequence confidence), the data completeness increases dramatically. Since the method presented here reduces the LC-MS/MS analysis from 3 h to 1 h and increases the number of phoshosites identified up to 10-fold in contrast to published studies in fungi, we pushed the phospho-proteomic technique beyond its current limits and could provide a sophisticated resource for investigation of signaling processes in filamentous fungi.

MzSTools is a plugin for QGIS developed by the Institute of Environmental Geology and Geoengineering of the National Research Council (CNR-IGAG). The plugin has been designed as a set of practical and easy-to-use tools to carry out seismic microzonation (SM) studies, by producing standard compliant geographic database and maps, thus making them accurate, homogeneous and uniform for all municipalities in Italy. A geodatabase based on SQLite/SpatiaLite Relational Database Management System (RDBMS) has been designed to collect and store data related to elements such as: geognostic surveys; bedrocks and cover terrains; superficial and buried geomorphological elements; tectonic-structural elements; elements of geological instability such as landslide zones, liquefaction zones and zones affected by active and capable faults; homogeneous microzones in seismic perspective, microzones characterized by a seismic amplification factor. MzSTools assembles in a single software environment a set of useful tools in a configurable QGIS project template, comprising layers, symbol libraries, cartographic styles and print layouts for the SM maps. The plugin is open source and hosted on the GitHub platform, and available via the official QGIS plugins repository (https://plugins.qgis.org/plugins/MzSTools/).

Bisphenol-A (BPA) represents an important co-monomer for obtaining polycarbonate, epoxy resins, flame retardants, in paint, and other chemicals products. Products containing BPA are widely used, and thus, we can find it in the environment: in the air, in the soil, in natural surface water and in sediments, underground water in landfills, and in wastewater. BPA disturbs human and animals’ health. This influences the enzymatic, androgenic, neurological, liver and reproductive systems at different stages of human life: like in fetal stage, children and adults’ stages. Taking these inconveniences into account, it is very important to remove BPA from water. Ultrasonic technology can be considered a verry sustainable and efficient method to remove BPA from water. The advantages of this method is easy to implement on existing water treatment and purification facilities, it does not produce residual compounds that produce sludge, the time required for degradation is of the order of 1-2 hours and the level of degradation is very high. In this work, we presented the studies on the efficiency of ultrasonics under air atmosphere on the degradation of BPA. The influence of the frequency and of some additional compounds such as carbon tetrachloride, FeSO4 7H2O (FS), and ethyl anthraquinone (EAC) was studied. Three different frequencies were used: 1146 KHz, 864 KHz, 580 KHz, at a power of 50 W. It was identified the efficiency of BPA degradation over a period of 60 minutes, with sampling every 15 minutes. Using the LC-MS/MS technique, the degradation compounds were identified that result from the application of ultrasound processes. Pathways of BPA degradation were also proposed.

in the following article I analyze the trend of cultural and creative employment in the Italian regions between 2004 and 2022 through the use of ISTAT-BES data. After presenting a static analysis, I also present the results of the clustering analysis aimed at identifying groupings between Italian regions. Subsequently, an econometric model is proposed for estimating the value of cultural and creative employment in the Italian regions. Finally, I compare various machine learning models for predicting the value of cultural and creative employment. The results are critically discussed through an economic policy analysis.

Classically the walk in biped robotics was obtained controlling balance during the whole step, i.e. guaranteeing that the pressure point under the soles always stayed in the polygon of the supporting feet. However, this assumed that the feet were able to transfer torque to the ground during the whole gait cycle. In spite of the fact that the amount of transferrable torque in the feet-ground contact is limited, it is possible only during some phases of the step, and the overall process is energetically inefficient. On the other side, starting from the passive motion of the rimless wheel falling on an inclined surface, and ending to the inverted pendulum with a compass, balance in the whole was proven in spite of dynamical instability inside each step. Along this line results of Foot Placement Estimation (FPE) in 2-D and 3-D showed how energy efficient walk was possible, emulating the human walk with a free fall on the swing foot and energy restitution at the foot collision with the ground for the next step. This model assumes pointy feet, so without torque transfer to the ground. In the realm of FPE, in previous papers the present author adopted the 3-D inverted pendulum in polar coordinates (Spherical Inverted Pendulum - SIP) to introduce omnidirectional walks with arbitrarily changing characteristics. No torque control was used during the step, i.e the pendulum was always in free fall at each step, the only control actions were at the beginning of the next step. These actions are: the change of angular velocities at the start of a new step, with respect to those given after the collision (emulating the torque action in the brief double stance period), to recover for the losses, and the preparation of the position in the frontal and sagittal planes of the swing foot for the next collision. The present paper improves this paradigm, proposing a general model to account for all characteristics of the biped and of the gait, with adding a minimum of dynamical complexity with respect to the SIP. This model allows, not only to walk omnidirectionally on a flat surface, but also to go up and down staircases.

The financial sector, too, is developing innovative services and products that have the potential to make a more positive impact on global environmental goals. However, research sheds little light on environmental attitudes and behavioral patterns of employees in this sector. There are multiple factors promoting or inhibiting environmental behavior. Those factors may be rooted in individual or subjective norms, but also social influence and to some extent financial incentives and benefits. A survey concerning the intention to improve and actually show ‘green behavior’ was developed based on widely used acceptance models which differentiate between desirable behavior and the intention to show such behavior. Employees are predominately responsive towards environmental behavior: 20% are convinced of the need to act in a “green” and sustainable manner, only 5% are hard to win over or are not accessible at all. Financial loss or benefits combined with social motives contribute to sustainable living whereas financial benefits alone actually hinder such behavior. The study underlines the existence of a intention-behavior gap: The intention to behave sustainably is built somewhat separately from various influences. There are moderating factors like sex, age and family status that influence the decisions. This then leads to a gap between intention and actual behavior.

Considering increasingly ambitious pledges by countries, pressure from society, investors, and clients further up the supply chain, the question for companies is not so much whether to take decarbonisation action, but what action and by when. However, determining an ideal mix of measures to apply ‘decarbonisation efficiency’ requires more than knowledge of technically feasible measures and how to combine them to achieve the most economic outcome: In this paper, the author describes seven aspects which heavily influence the composition of an ‘ideal mix’ that executive leadership needs to take a (strategic) position on. These aspects consider underlying motivations and span across (socio-)economic, technical, regulatory, strategic, corporate culture and environmental factors and further underline the necessity of clarity of definitions. How these decisions influence the determination of the decarbonisation-efficient ideal mix of measures, both in principle but also in terms of specific impact is further explored by providing examples. What choices are taken by German manufacturers in several of the aspects is disclosed by insights from about 850 responses to the ‘Energy Efficiency Index of German Industry’. Knowledge of the status quo, and clarity in definitions, objectives, time frames and scope are key.

The leather industry is one of the most polluting industries in the world due to the large amounts of waste following the raw hides processing, but also due to the high content of chemicals present in their composition. The main problem of chromium-tanned leather solid waste is related to their storage, because of the ability of chromium to leach in soil or water, and also owing to the high ability of trivalent chromium to oxidize to its toxic form, hexavalent chromium. The purpose of this study is to present the latest methods for extracting trivalent chromium from the composition of solid leather wastes. The extraction methods identified in the present study are based on acid/basic/enzymatic hydrolysis and substitution with the help of organic chelators (organic acids and organic acid salts). In addition, the study includes a comparative analysis between the advantages and disadvantages of each identified extraction method. At the same time, the study also presentes alternative chromium extraction methods based on the combination of conventional extraction methods and ultrasound-assisted extraction.

(1) Background: Considering highly selected patients with ductal carcinoma in situ (DCIS), active surveillance is a valid alternative to surgery. Our study is aimed at showing the reliability of post-biopsy complete lesion removal, documented by mammogram, as additional criterion to select these patients. (2) Methods: 2173 Vacuum Assisted Breast Biopsies (VABB) documented as DCIS have been reviewed. Surgery has been performed in all cases. We retrospectively collected the reports of post-VABB complete lesion removal and the histological results of the biopsy and surgery. We calculated the rate of upgrade of DCIS identified on VABB upon excision for patients with post-biopsy complete lesion removal and for those showing residual lesion. (3) Results: We observed 2173 cases of DCIS: 408 classified as low grade; 1262 as intermediate grade; 503 as high grade. The overall upgrading rate to invasive carcinoma was 15.2% (330/2173). The upgrade rate was significantly lower (8.2%) when considering patients showing mammographically documented complete removal of the lesion. (4) Conclusion: The absence of mammographically documented residual lesion following VABB is associated to a lower upgrading rate of DCIS to invasive carcinoma on surgical excision and should be considered when deciding the proper management DCIS diagnosis.

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Sorption of pure CO2 and CH4 and CO2/CH4 binary gas mixtures in amorphous glassy Poly(2,6-dimethyl-1,4-phenylene) oxide (PPO) at 35°C up to 1000 Torr is investigated. Sorption experiments were carried out using an approach that combines barometry with FTIR spectroscopy in the transmission mode to quantify the sorption of pure and mixed gases in polymers. The pressure range is chosen to prevent any variation of the glassy polymer density. The solubility within the polymer of the CO2 present in the gaseous binary mixtures is practically coincident with the solubility of pure gaseous CO2, up to a total pressure of the gaseous mixtures equal to 1000 Torr and for CO2 mole fraction of ~0.5 mol mol-1 and ~0.3 mol mol-1. The Non-Equilibrium Thermodynamics for Glassy Polymers (NET-GP) modelling approach has been applied to the Non-Random Hydrogen Bonding (NRHB) lattice fluid model to fit the solubility data of pure gases. We have assumed here that no specific interactions are occurring between the matrix and the absorbed gas. The same thermodynamic approach has been then used to predict the solubility of CO2/CH4 mixed gases in PPO resulting in a deviation lower than 9.5% from the experimental results for CO2 solubility.

The wind industry is looking for ways to accurately predict the reliability and availability of newly installed wind turbines. Failure modes, effects and criticality analysis (FMECA) is a technique utilized for determining the critical subsystems of wind turbines. There are several studies which applied FMECA for wind turbines in the literature, but no studies so far have considered different weather conditions or climatic regions. Furthermore, various design types of wind turbines have been analyzed applying FMECA but no study so far has applied FMECA to compare the reliability of geared and direct-drive wind turbines. We propose to fill these gaps by using Koppen-Geiger climatic regions and two different turbine models of direct-drive and geared-drive concepts. A case study is applied on German wind farms utilizing the WMEP database which contains wind turbine failure data from 1989 to 2008. This proposed methodology increases the accuracy of reliability and availability predictions and compares different wind turbine design types and eliminates underestimation of impacts of different weather conditions.

A Digital Twin (DT) refers to a virtual representation or digital replica of a physical object, system, process, or entity. This concept involves creating a detailed, real-time digital counterpart that mimics the behavior, characteristics, and attributes of its physical counterpart. DTs have the potential to improve efficiency, reduce costs, and enhance decision-making by providing a detailed, real-time understanding of the physical systems they represent. While this technology is finding application in numerous fields, such as energy, healthcare, transportation, it appears to be a key component of the digital transformation of industries. In this paper, we present the research results achieved by IoTwins, a European research project aimed at investigating opportunities and issues of adopting DTs in the fields of industrial manufacturing and facility management. Particularly, we discuss a DT model and a reference architecture for use by the research community to implement a platform for the development and deployment of industrial DTs in the cloud continuum. Guided by the devised architectures’ principles, we implemented an open platform and a development methodology to help companies build DT-based industrial applications and deploy them in the so-called Edge/Cloud continuum. To prove the research value and the usability of the implemented platform, we discuss a simple yet practical development use case.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.

Background: Swimming and, specifically, front crawl, can be included among the "overhead" sports. Overhead sports are a risk factor for some problems of the musculoskeletal system, especially the shoulder. The aim of the study was assessing the incidence of shoulder and neck pain in a Masters Swimming Team and its correlation with the crawl stroke. Methods: It is an observational study through video-analysis of the stroke and a questionnaire. The participants are 61 athletes of a Master team, whose prevailing training stroke was the front crawl were selected for the present study. Their stroke was analyzed during training by a go-pro camera mounted on a sliding trolley on a track, evaluating with their trainer their technical defects. A questionnaire about frequency of shoulder and neck pain during the last five years was administered to all the participants at the study. Results: From the questionnaire, 45 and 55 out of 61 athletes had suffered from shoulder pain and cervical pain, respectively. Both types of pain were correlated with the weekly swimming volume. The swimmers with hyperflexion of the wrist and prolonged internal rotation in the pulling phase had shoulder problems. Those who suffered from current shoulder pain reduced the underwater time. The four swimmers with an excessive body roll during breathing and those who kept their heads extended, reported cervical pain. Conclusions: Shoulder and neck pain could be prevented with the correction of specific technical errors in crawl stroke.

We prove a version of Ekeland Variational Principle (EkVP) in a weighted graph $G$ and its equivalence to Caristi fixed point theorem and to Takahashi minimization principle. The usual completeness and topological notions are replaced with some weaker versions expressed in terms of the graph $G$. The main tool used in the proof is the OSC property for sequences in a graph. Converse results, meaning the completeness of graphs for which one of these principles holds is also considered.

Different external stimuli are perceived by multiple sensor histidine kinases and transmitted by phosphorylation via the phosphotransfer protein Ypd1p in the multistep phosphorelay system of the high osmolarity glycerol signaling pathway of filamentous fungi. How the signal propagation takes place is still not known in detail, since multiple sensor histidine kinase genes in most filamentous fungi are coded in the genome, whereas only one gene for Ypd1 exists. That raises the hypothesis that various Ypd1 isoforms are produced from a single gene sequence, perhaps by alternative splicing, facilitating a higher variability in signal transduction. We found that the mRNA of MoYPD1 in the rice blast fungus Magnaporthe oryzae is subjected to an increased structural variation and amplified putative isoforms on a cDNA level. We then generated mutant strains overexpressing these isoforms, purified the products and present here one previously unknown MoYpd1 isoform on a proteome level. Alternative splicing was found to be a valid molecular mechanism to increase the signal diversity in eukaryotic multistep phosphorelay systems.

The introduction of the Internet of Things (IoT), i.e. the interconnection of embedded devices over the Internet, has changed the world we live in from the way we measure, make calls, print information and even the way we get energy in our offices or homes. The convenience of IoT products, like CCTV cameras, IP phones, and oscilloscopes, is overwhelming for end-users. In parallel, however, security issues have emerged and it is essential for infrastructure providers to assess the associated security risks. In this paper, we propose a novel method to detect IoT devices and identify the manufacturer, device model, and the firmware version currently running on the device using the page source from the web user interface. We performed automatic scans of the large-scale network at the European Organization for Nuclear Research (CERN) to evaluate our approach. Our tools identified 233 IoT devices that fell into eleven distinct device categories and included 49 device models manufactured by 26 vendors from across the world.

Patients with Multiple Myeloma have an increased susceptibility to severe infections due to several various factors, especially the high tumor burden. The use of the anti-CD38 monoclonal antibodies-based therapies has changed the frequency and epidemiology of infections. We report herein the safety profile of the pivotal clinical trials conducted with anti-CD38 mAbs (daratumumab and isatuximab) and anti-SLAMF7 mAbs (elotuzumab) that led to the approval of regimens employed today in NDMM and RRMM patients.

BACKGROUND Relaxin (RLX), a hormone-like molecule with pleiotropic effects, has been found to reduce matrix deposition and mediate collagen degradation in animal models of chronic liver injuries and might be considered as an adjuvant therapeutic agent for progressive liver diseases. AIMS In the present study, we evaluated whether RLX affects the development of liver fibrosis in an experimental mouse model of NASH in C57BL6 male mice fed with a methionine-choline deficient diet (MCD). Methods Mice were treated per os as we intended to assess the enteric absorption and bioavailability of orally administered RLX (RLX purified from pig ovaries, IBSA SA, Lugano, Switzerland). Mice were fed the MCD diet for 6 weeks. After the initial 3 weeks, one group received drinking water supplemented with RLX (25 mcg/ml) whereas the other continued to receive regular water. A third group of mice fed a regular diet served as control. After 3 additional weeks mice were anesthetized and sacrificed. Results A significant, reduced expression of the pro-inflammatory cytokines TNF-α and of relevant markers of active fibrogenesis and extracellular matrix deposition, Col1A1 and α-SMA, was observed in mice treated with RLX vs controls. RLX also induced a significant decrease of TIMP1 and an increase of both MMP 2 and 9 when evaluated by zymographic analysis in liver extracts. Conclusions Although preliminary pharmacokinetics experiments showed barely detectable amounts of RLX in the blood of mice treated per os, these data support the absorption of orally administered RLX and confirm its potential therapeutic use in the management of liver fibrosis.

In this paper we overview all analytical engineering solutions for corrosion problems in pressure vessels delivered over the past 60 years. We briefly detail strengths and weaknesses of existing approaches, thus demonstrating the need for novel uniform corrosion analysis methods for both current and new applications. To complement the review, we also present a new analytical model allowing to estimate the lifetime of pressured elastic vessels with mechanically assisted corrosion. Both internal/external pressure and internal/external corrosion are captured and dissolution driven corrosion is also considered. The readily implemented method improves existing analytical approaches and is shown to be effective for thin and thick shells, as well as various loading and corrosion intensity and geometrical conditions.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

Optimization of post polymerization processing of polyolefin elastomers (POE) is of considerable industrial interest. To this aim, experimental determination and theoretical interpretation of the thermodynamics and mass transport properties of POE-solvent mixtures is relevant. Sorption behaviour of n-hexane vapour in a commercial propylene-ethylene elastomer (V8880 VistamaxxTM from ExxonMobil) is addressed here, determining experimentally the sorption isotherms at temperatures ranging from 115 to 140 °C and pressure values of n-hexane vapour up to 1 atm. Sorption isotherms have been interpreted with the Non-Random-Hydrogen-Bonding Equation of State model retrieving, from data fitting, the value of the binary interaction parameter for the n-hexane/V8880 system. Both the case of temperature-independent and of temperature-dependent binary interaction parameter have been considered. Sorption kinetics was also investigated at different pressures and has been interpreted using a Fick’s model determining values of the mutual diffusivity as a function of temperature and of n-hexane/V8880 mixture composition. From these values, n-hexane intra-diffusion coefficient has been calculated interpreting its dependence on mixture concentration and temperature by a semi-empiric model based on free volume arguments.

In implantology, among the key choices, to obtain predictable results, it’s essential to establish, using CBCT, the bone site where to insert the implants; these sites must be identified on the mucosa and secondarily, during the surgical phase, on the cortical bone. Surgical templates are a valid aid especially in complex cases which require sev-eral implants. In cases of single implant, on the other hand, surgical guides are rarely used and the implant is inserted freehand and the identification of the implant site on the oral mucosa is more difficult; for this reason the clinician uses the teeth in the arch as a ref-erence. This experimental study is based on the use of a thermo-printed mask, con-taining radiopaque references which, worn by edentulous patients during the execu-tion of the CBCT, helps to evaluate the identification of the implant sites on the patient when surgical guides are not used and the free hand technique is adopted. This method is certainly reserved for experienced operators capable of identifying the correct angle of the implants with the freehand technique. The level of experience remains fundamental in the clinician's decision whether or not to use surgical guides; in fact, doctors with little experience should use surgical guides even in the simplest cases to reduce the risk of error.

In implantology, among the key choices, to obtain predictable results, it is essential to establish, on the basis of radiographic examinations, the bone site where to insert the implants; these selected locations must be identified first on the mucosa and then on the cortical bone. Surgical guides represent a valid aid especially in complex cases with more than 3 or 4 implants, whereas in single implant cases they are rarely used. This study evaluates the clinical precision with which the implant sites, on the patient's mucosa, are identified in surgical procedures planned without any templates. The verification of this precision is carried out through thermo-printed templates with radiopaque references which could however help the clinician to identify these sites in a simple, rapid and economical way.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

Ground-based high-power lasers enable to, in principle, deorbit any kind of space debris object from the low Earth orbit (LEO) by remotely inducing laser-ablative momentum. However, the assessment of efficiency and operational safety depends on many factors like atmospheric constraints or the risk of debris disintegration during irradiation. We analyze laser momentum for a great variety of target geometries and sizes, and – for the first time in a large-scale simulation – include thermal constraints for laser irradiation configuration. Using a coherently coupled 100 kJ laser system at 1030 nm wavelength, 5 ns pulse duration in an optimized pointing elevation angle range, the pulse frequency should amount to less than 10 Hz to prevent fragment meltdown. For mechanically intact payloads or rocket bodies, repetition rates should be even lower. Small debris fragments sized between 10 and 40 cm can be de-orbited by around 100 to 400 station passes with head-on irradiation while objects exceeding 2 m typically require far more than 1000 irradiations for deorbit. Hence, laser-based debris removal cannot be considered a prime space sustainability measure tackling the top-risk large debris, yet it can provide for remediation of a multitude of small-sized debris using small networks of globally distributed laser sites.

We derive the stabiliser group of the four-vector, also known as Wigner’s little group, in case of massless particle states, as the maximal solvable subgroup of the proper orthochronous Lorentz group of dimension four, known as the Borel subgroup. In the absence of mass, particle states are disentangled into left and right handed chiral states, governed by the maximal solvable subgroups sol2± of order two. Induced Lorentz transformations are constructed and applied to general representations of particle states. Finally, it is argued how the spin-flip contribution is closely related to the occurrence of nonphysical spin operators.

The New World (NW) mammarenavirus group includes several zoonotic highly pathogenic viruses, such as Junin (JUNV) or Machupo (MACV). Contrary to Old World mammarenavirus, these viruses are not able to completely suppress the innate immune response, and trigger a robust interferon (IFN)-I response via retinoic acid-inducible gene I (RIG-I). Nevertheless, pathogenic NW mammarenaviruses trigger a weaker IFN response than their non-pathogenic relatives do. RIG-I activation leads to upregulation of a plethora of IFN-stimulated genes (ISGs), which exert a characteristic antiviral effect either as lone effectors, or resulting from the combination with other ISGs or cellular factors. The dsRNA sensor-protein kinase receptor (PKR) is an ISG that plays a pivotal role in the control of the mammarenavirus infection. In addition to its well-known protein synthesis inhibition, PKR further modulates the overall IFN-I response against different viruses, including mammarenaviruses. For this study, we employed Tacaribe virus (TCRV), the closest relative of the human pathogenic JUNV. Our findings indicate that PKR does not only increase IFN-I expression against TCRV infection, but also affects the kinetic expression and the extent of induction of Mx1 and ISG15 at both levels, mRNA and protein expression. Moreover, TCRV fails to prevent the effect of PKR on viral protein translation and its viral titer is inhibited when PKR is pre-stimulated via IFN-I. Here, we provide first evidence of the specific immunomodulatory role of PKR over selected ISGs, altering the dynamic of the innate immune response course against TCRV. IMPORTANCE: The mechanisms for innate immune evasion are key for emergence and adaptation of human pathogenic arenaviruses, and highly pathogenic mammarenaviruses such as JUNV or MACV trigger a weaker IFN response than non-pathogenic mammarenaviruses. Within the innate immune response context, PKR plays an important role in sensing and restricting the infection of TCRV virus. Although the mechanism of PKR for protein synthesis inhibition is well described, its immunomodulatory role is less understood. In this study, we found that TCRV protein expression and viral propagation are inhibited from early times after infection, and when externally activated, PKR inhibits TCRV viral progeny production. Our present findings further characterize the innate immune response in absence of PKR, unveiling the role of PKR in defining the ISG profile after viral infection.

The group III two-component hybrid histidine kinase MoHik1p in the filamentous fungus Magnaporthe oryzae is known to be a sensor for external osmotic stress and essential for the fungicidal activity of the phenylpyrrole fludioxonil. The mode of action of fludioxonil has not yet been completely clarified but rather assumed to hyperactivate the high osmolarity glycerol (HOG) signaling pathway. To date, not much is known about the detailed molecular mechanism of how osmotic stress is detected or fungicidal activity is initiated within the HOG pathway. The molecular mechanism of signaling was studied using a mutant strain in which the HisKA signaling domain was modified by an amino acid change of histidine H736 to alanine A736. We found that MoHik1pH736A is as resistant to fludioxonil but not as sensitive to osmotic stress as the null mutant ∆Mohik1. H736 is required for fludioxonil action but is not essential for sensing sorbitol stress. Consequently, this report provides evidence of the difference in the molecular mechanism of fludioxonil action and the perception of osmotic stress. This is an excellent basis to understand the successful phenylpyrrole-fungicides’ mode of action better and will give new ideas to decipher cellular signaling mechanisms.

Tree species composition is an important key element for biodiversity and sustainable forest management, and hyperspectral data provide detailed spectral information, which can be used for tree species classification. There are two main challenges for using hyperspectral imagery: a) Hughes phenomena, meaning by increasing the number of bands in hyperspectral imagery, the number of required classification samples would increase exponentially, and b) in a more complex environment, such as riparian mixed forest, focusing on spectral variability per pixel may not be adequate for definability of tree species. Therefore, the focus of this study is to assess spectral-spatial dimensionality reduction of airborne hyperspectral imagery by using minim noise fraction (MNF) transformation, and object-based image analysis (OBIA). An airborne prism experiment (APEX) hyperspectral imagery was used. A study area was a riparian mixed forest located along the Salzach river, and six tree species including Picea abies, Populus (canadensis and balsamifera), Fraxinus excelsior, Alnus incana, and Salix alba were selected. A machine learning algorithm random forest (RF) was used to train and apply a prediction model for classification. Using a spectral dimensionality reduced APEX, a pixel-level classification was also done. According to a confusion matrix, the object-level classification of MNF-derived components achieved the overall accuracy of 85 %, and kappa coefficient of 0.805. The performance of classes according to producer’s accuracy varied between 80% for Fraxinus excelsior, Alnus incana, and Populus canadensis to 90% for Salix alba and Picea abies. Comparison the results to a pixel-level classification, showed a better performance of object-level classification (an overall accuracy of 63% and Kappa coefficient of 0.559 were achieved for pixel-level classification). The performance of classes using pixel-based classification varied 45 % for Alnus incana to 80% for Picea abies. In general, Spectral-spatial complexity reduction using MNF transformation and object-level classification yielded a statistically satisfactory results.

(1) Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this study is to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. (2) The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett's formula. (3) Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. 14% of the sample (23 patients) showed a prolongation of the QTc interval. 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone: in 90% of these patients, a normalization in the QTc length was established. (4) This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of a careful electrocardiographic monitoring in methadone-treated patients.

Industrial data scarcity is one of the largest factors holding back the widespread use of machine learning in manufacturing. To overcome this problem, the concept of transfer learning was developed and it achieved high attention in recent industrial research. Our paper focuses on the problem of time series segmentation and presents the first in-depth research about transfer learning for deep-learning based time series segmentation on the example of industrial end-of-line pump testing. In particularly, we investigate if the performance of deep learning models can be increased by pretraining the network with data from other domains. Three different scenarios are analyzed: source and target data being closely related, source and target data being distantly related, and source and target data being non-related. The results demonstrate that transfer learning can enhance the performance of time series segmentation models in respect to accuracy and training speed. The benefit is most clearly seen in scenarios where source and training data are closely related and the number of target training data samples is lowest. However, in the scenario of non-related datasets, cases of negative Transfer Learning were observed as well. Thus, the research emphasizes the potential, but also the challenges of industrial Transfer Learning.

Reinforced concrete (RC) columns are often placed under confinement to increase their strength and ductility. Carbon fiber reinforced polymer (CFRP) materials have recently been recognized as favorable confinement systems. At present, a number of national standards and codes dedicated to the design of concrete components strengthened with CFRP in general and CFRP confinement in particular are available. These sets of rules provide design equations for confined reinforced concrete columns with circular and rectangular cross sections. Most of the standards and codes exhibit significant differences, including the used predictive models limitations, observed effects, and covered loading conditions. In this paper, five international standards and design guidelines are introduced and discussed. The purpose is to present a constructive and critical assessment of the state-of-the-art design methodologies available for CFRP confined RC columns and to discuss effects not previously considered properly. Therefore, some recent research efforts and findings from the Leipzig University of Applied Sciences are also introduced. The obtained data is used for a comparative study of the guideline predictive equations. Furthermore, it is shown that some new findings concerning the rupture strength and the maximum strength plus accompanying axial strain of a CFRP confined column are suitable to improve the current guidelines.

Bisphenol A is a remarkable chemical compound for its many applications mainly in the plastics industry, but also for its toxic effects on the environment and human health. BPA (4,4-isopropylidenediphenol) is an anthropogenic compound, moderately soluble in water (120 – 300 mg/l) at room temperature, and highly soluble in alkaline solutions, ethanol and acetone. BPA can bioconcentrate, bioaccumulate and biomagnify through food webs until it reaches humans. To prevent this, effective strategies are sought to allow its removal from the environment, through physico-chemical or enzymatic methods, advanced oxidation, adsorption and biodegradation, ultrasonic degradation. This article shows a comparative study regarding adsorption of BPA on Active carbon and zeolitic tuff, ZTC. In this paper, the characterization of the zeolitic tuff Rupea adsorbent, was carried out from an elemental and mineralogical point of view, pore size and elemental distribution, using SEM, EDAX, and XRD analysis. The pore size varies from 30 nm to 10 µm, atomic ratio Si/Al≥4, and the 80 % of mineralogical composition represent Ca Clinoptilolite zeolites Ca Clinoptilolite zeolite ((Na1.32K1.28Ca1.72Mg0.52)(Al6.77Si29.23O72)(H2O)26.84). Also, a comparative study of the adsorbtion capacity of bisphenol A from synthetic solutions on activated carbon type - Norit GAC 830 W, GAC, as well as on Clinoptilolite-type zeolitic tuff, ZTC, Rupea, was carried out. The experiments were carried out at a temperature of 20 ºC, a pH of 4.11; 6.98 and 8.12, and ionic strength being assured using KCl of 0.01 M, and 0.1 M. The adsorption capacities of GAC and ZTC tend to 115 mg/g and 50 mg/g respectively, at 8.12 pH and ionic strength of 0 M. The Langmuir mathematical model most faithfully describes the adsorption equilibrium of BPA. The maximum adsorption capacity for both adsorbents increases with increasing pH, and decreases with increasing ionic strength.

Graphs are largely used in computer science to model relations, or associations, among entities the compose complex systems. More recently, they found a broad field of application in bioinformatics and medical informatics supporting modelling, analysis of many systems. The applications span from representing interactions among molecules within cells, to model the functions of the brains. In order to support research, algorithms from graph theory that are able to extract knowledge from network should be coupled to efficient visualisation techniques. Although the importance of such topic, we retain that many challenges should be faced in the futures, such as automated pathway and network layout to better match biologists’ needs, the developing of a standard able to give more and better choices to represent nodes, edges finally, the developing of automated mechanism able to improve the network navigation methods that help users manage large and complex networks with the goal to improve the usability.

In the following article, we estimate the Renunciation of Healthcare Services-RHS in Italian regions in the context of the Environmental, Social and Governance-ESG model during the period 2004-2022. The data were acquired from the ISTAT-BES dataset. The data were analyzed using the following econometric techniques: Panel Data with Fixed Effects, Panel Data with Random Effects, Pooled Ordinary Least Squares-OLS, Weighted Least Square-WLS,. Results show that RHS tends to growth with the E-Component, is negatively associated to the S-Component, and positively associate with the G-Component within the ESG model. Furthermore, a clusterization with the unsupervised k-Means algorithm is presented and the results are discussed with a confrontation between optimal and suboptimal k values optimized with the Silhouette Coefficient. Finally, a confrontation among eight different machine-learning algorithms is performed to predict the future value of RHS. Outcomes show that the Simple Regression Tree is the best predictive algorithm and that the level of RHS is predicted to growth on average of 4.4% for the Italian regions. Results are critically discussed.

Key genes needed for maintenance and growth for the two pathogens, Fusarium graminearum and Magnaporthe oryzae, were identified. These are genes that are induced in response to maintenance requirements (stress) and growth requirements. The processes involved are synthesizing arginine, synthesis of DNA-bases, nitric oxide synthesis needing arginine, autophagy, DNA synthesis, and DNA repair. A simplified regulatory network for these key genes for both organisms was constructed as a hypothesis for the work, and procedures previously developed to use sets of downloaded transcriptomic data were used to test hypotheses concerning what time under the course of infection of plants the key genes are expressed. The analysis shows that the transcription efforts (costs) to maintain the fungal cells (maintenance) are high before infection and during early infection. During the following biotrophic stage, maintenance activities drop, followed by a dramatic increase in the necrotrophic stage transition. Finally, in the necrotrophic stage, maintenance is again lower despite the high growth rate that can also cause stress. All identified genes' expressions behaved almost similar with an increased expression in the biotrophy-necrotrophy transition for both fungi except the DNA repair genes PARP/PARG that was not responding or absent (PARG) in the mainly clonal M. oryzae. This PARG expression pattern might indicate that M. oryzae is more subject to evolution by point mutations than F. graminearum, where sexual reproduction is frequent. The potential consequences of this in the development and the accelerated breakage of host species resistance in a Red Queen dynamics scenario are discussed. The analysis demonstrates the possibility of using large transcriptome datasets and co-regulations between key genes to test hypotheses. This technique's advantages complement molecular techniques that employ knockouts and over-expression of target genes to suggest that genes' roles are discussed.

Although the idea of making electric weapons has emerged since the beginning of the 20th Century, the great number of technological problems made that such technology was not developed. During the Cold War, the US strategic programme Space Defensive Initiative paid a special attention to this category of weapons, but the experiments have demonstrated that the prototypes are too big, very heavy, and involve a very high energy consumption and low reliability. Under these circumstances, the authors have noticed the trend to design new types of electric weapons starting from the hybridization of some technologies: the compressed flux weapons, the plasma electromagnetic cannon, the electromagnetic weapons as the coil-gun and rail-gun.

In this work we report on our effort to design and implement an early introduction to basic robotics principles for children at kindergarten age. The humanoid robot Pepper, which is a great platform for human-robot interaction experiments, was presenting the lecture by reading out the contents to the children making use of its speech synthesis capability. One of the main challenges of this effort was to explain complex robotics contents in a way that pre-school children could follow the basic principles and ideas using examples from their world of experience. A quiz in a Runaround-game-show style after the lecture activated the children to recap the contents they acquired about how mobile robots work in principle. Besides the thrill being exposed to a mobile robot that would also react to the children, they were very excited and at the same time very concentrated. What sets apart our effort from other work is that part of the lecturing is actually done by a robot itself and that a quiz at the end of the lesson is done using robots as well. To the best of our knowledge this is one of only few attempts to use Pepper not as a tele-teaching tool, but as the teacher itself in order to engage pre-school children with complex robotics contents. We got very positive feedback from the children as well as from their educators.

In thermal power plants equipped with air-cooled condensers, axial cooling fans operate under the influence of ambient flow fields. Under inlet cross-flow conditions, the resultant asymmetric flow field is known to introduce additional harmonic forces to the fan blades. This effect has previously been studied only numerically or using blade mounted strain gauges. For this study, Laser Scanning Vibrometry was used to assess fan blade vibration under inlet cross-flow conditions in an adapted fan test rig inside a wind tunnel test section. Two co-rotating laser beams scanned a low pressure axial fan, resulting in spectral, phase resolved surface vibration patterns of the fan blades. Two distinct operating points were examined, with and without inlet cross-flow influence. While almost identical fan vibration patterns were found for both reference operating points, overall blade vibration increased by 100% at low fan flow rate due to cross-flow, and by 20% at high fan flow rate. While numerically predicted natural frequency modes could be confirmed from experimental data as minor peaks in the vibration amplitude spectrum, they were not excited significantly by cross-flow. Instead, primarily higher rotation rate harmonics were amplified, i.a. a synchronous blade tip flapping was strongly excited at the blade pass frequency.

Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 are showing promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled through modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and discuss how these mechanisms could inspire or improve anticancer therapies.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

As of today, 20 disease modifying drugs (DMD) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgement and experience of neurologists and the evaluation of therapeutic response can only be obtained by monitoring clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, the aim of this study is to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing-remitting courses. These patients were characterized on the basis of their age, sex, presence of oligoclonal bands, therapy and MRI lesion load at onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data we generated a few simulation scenarios for each patient, including those who matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which really occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment.

We constructed a novel design integrating the administration of a clinical self-assessment scale with simultaneous acquisition of functional Magnetic Resonance Imaging (fMRI), aiming at cross-validation between psychopathology evaluation and neuroimaging techniques. We hypothesized that areas demonstrating differential activation in two groups of patients (paranoid and depressive) will have distinct connectivity patterns and structural differences.

Timely and accurate identification of change detection for areas depicted on nautical charts constitutes a key task for marine cartographic agencies in supporting maritime safety. Such a task is usually achieved through manual or semi-automated processes, based on best practices developed over the years requiring a substantial level of human commitment (i.e., to visually compare the chart with the new collected data or to analyze the result of intermediate products). This work describes an algorithm that aims to largely automate the change identification process as well as to reduce its subjective component. Through the selective derivation of a set of depth points from a nautical chart, a triangulated irregular network is created to apply a preliminary tilted-triangle test to all the input survey soundings. Given the complexity of a modern nautical chart, a set of feature-specific, point-in-polygon tests are then performed. As output, the algorithm provides danger-to-navigation candidates, chart discrepancies, and a subset of features that requires human evaluation. The algorithm has been successfully tested with real-world electronic navigational charts and survey datasets. In parallel to the research development, a prototype application implementing the algorithm was created and made publicly available.

Mate choice that is based on behavioural traits is a common feature in the animal kingdom. Using the Trinidadian guppy, a species with mutual mate choice, we investigated whether males use female swimming activity – a behavioural trait known to differ consistently among individuals in many species – as a trait relevant for their mate choice. In a first experiment, we assessed male and female activity in an open field test alone (two repeated measures) and afterwards in heterosexual pairs (two repeated measures). In these pairs, we simultaneously assessed males’ mating efforts by counting number of sexual behaviours (courtship displays and copulation). Male and female guppies showed consistent individual differences in their swimming activity when tested both alone and in a pair, and these differences were maintained across both test situations. When controlling for male swimming behaviour and both male and female body size, males performed more courtship displays towards females with higher swimming activity. In a second experiment, we tested for a directional male preference for swimming activity by presenting males video animations of low and high active females in a dichotomous choice test. In congruence with experiment 1, we found males to spend significantly more time in association with the high active female stimulus. Both experiments thus point towards a directional male preference for higher activity levels in females. We discuss the adaptive significance of this preference as activity patterns might indicate individual female quality, health or reproductive state while, mechanistically, females that are more active might be more detectable to males as well.

Regeneration of peripheral nerves depends on the ability of axons to navigate through an altered extracellular environment. It has been suggested that Schwann cells facilitate this process through their secretion of neuropeptides and proteases. Using the RT4-D6P2T Schwann cell line (RT4), we have previously shown that RT4 cultures endogenously express the neuropeptide PACAP, and respond to exogenous stimulation by inducing the expression of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) through PAC1 receptor activation. In this study, based on recent findings showing that doxycycline and minocycline act as positive allosteric modulators (PAMs) of the PAC1 receptor, we tested if treatment with these tetracyclines could induce the expression and activity of tPA and uPA in RT4 cells. Using ELISA and zymographic analyses, we demonstrate that doxycycline and minocycline reliably induce the secretion and activity of both tPA and uPA, which is paralleled by an increased expression levels, as shown by immunocytochemistry and Western blots. These actions were mediated, at least in part, by the PAC1 receptor, as PACAP6-38 mitigated tetracycline-induced expression and activity of tPA and uPA. We conclude that doxycycline and minocycline can act as PAMs of the PAC1 receptor to promote proteolytic activity in RT4 cells.

(1) Background: The interplay between coronavirus disease 2019 (COVID-19) and laryngeal cancer represents a substantial challenge for both patients and healthcare. To garner information on recent mortality data for laryngeal cancer, including during the COVID-19 pandemic, we analyzed real-world data from the US Centers for Disease Control and Prevention (CDC). (2) Methods: We searched the CDC WONDER on-line database 2018-2022 using with the ICD-10 code for laryngeal cancer (C32; malignant neoplasm of larynx). We also performed a sub-analysis between genders, and across ten-year age groups. Data were analyzed with one-way analysis of variance (ANOVA) and Tukey post-hoc test. (3) Results: The trend of age-adjusted mortality ×100,000 did not change significantly between 2018-2022 (p=0.553). Males had higher age-adjusted mortality rates (M/F ratios between 4.6 and 5.0), but no significant variation was found in both genders (males: p=0.676; females: p=0.596). Although the mortality rate remained unchanged in people aged 35-84 years, the variation reached statistical significance in those aged 85 or older (p=0.004), displaying significant increase in 2021 compared to 2018 (p=0.006) and 2019 (p=0.039). (4) Conclusions: The impact of the COVID-19 pandemic on mortality for laryngeal cancer seemed to be relatively modest in the general US population. Nevertheless, closer attention must be paid to older people, in whom the unfavorable consequences of misdiagnosis or mistreating can be exacerbated.

Over the years, network analysis became a promising strategy to analyze complex system, i.e. systems composed by a large number of interacting elements. In particular, multilayer networks have emerged as a powerful framework for modelling and analysing complex systems with multiple types of interactions. Network analysis can be applied to pharmacogenomics to gain insights into the interactions between genes, drugs, and diseases. By integrating network analysis techniques with pharmacogenomic data, the goal consists to uncover complex relationships and identify key genes to use in pathway enrichment analysis to figure out biological pathways involved in drug response and adverse reactions. In this study, we model omics, diseases and drugs data together through the multilayer network representation. Then, we mined the multilayer network with a community detection algorithm by obtaining top communities. After that, we used the identified list of genes from the communities to perform pathway enrichment analysis (PEA) to figure out the biological function affected form the selected genes. The results show that the genes forming the top community have the multiple roles through different pathways.

The Myb family of transcription factors (TFs) is a large and functionally diverse group found in all eukaryotes, but its role in fungi remains poorly understood. Here, we characterized a Myb family TF called MoMyb13 in the rice blast fungus, Magnaporthe oryzae. MoMyb13 has two Myb domains and has orthologues only in ascomycete fungi. Localization experiments confirmed that MoMyb13 is located in the nuclei, as expected for a TF. Phenotypic analysis showed that MoMyb13 mutants exhibited reduced growth, whitened colony appearance and no conidia formation. Importantly, these mutants completely lost pathogenicity, despite being able to form appressoria at their hyphae ends, suggesting that these appressoria were non-functional for causing infection. Furthermore, the mutant colonies lost hydrophobicity and had significantly reduced expression of the hydrophobin MPG1. However, overexpression of MPG1 in the mutants restored their hydrophobicity, but not pathogenicity. Stress assay showed that the mutants were more sensitive to SDS, CR and H2O2, but more tolerant to NaCl and SOR. In summary, our study revealed the essential role of the MoMyb13 in the growth, conidiation, hydrophobicity, stress response and pathogenicity of M. oryzae, and provides valuable insights into the working mechanism of Myb TFs in fungi.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

The following article analyzes Italian companies with more than 10 employees that use online sales tools. The data used were acquired from the ISTAT-BES database. The article first presents a static analysis of the data aimed at framing the phenomenon in the context of Italian regional disparities. Subsequently, a clustering with k-Means algorithm is proposed by comparing the Silhouette coefficient and the Elbow method. The investigation of the innovative and technological determinants of the observed variable is carried out through the application of a panel econometric model. Finally, different machine learning algorithms for prediction are compared. The results are critically discussed with economic policy suggestions.

In the following article I analyze the determinants of regular internet users in the Italian regions. The data is analyzed both in terms of static analysis and also through the application of the k-Means algorithm optimized with the Elbow method. Subsequently, an econometric model is presented for estimating regular internet users in the Italian regions based on variables that reflect the state of technological innovation and digital culture. The results are analyzed and discussed in light of the implications that digitalisation has for triggering economic growth.

In the following article I take into consideration the role of knowledge workers in the Italian regions. The analysed data refers to the ISTAT-BES database. The metric analysis consists of an in-depth analysis of the trends of the regions and macro-regions, followed by clustering with the k-Means algorithm, the application of machine learning algorithms for prediction, and the presentation of an econometric model with panel methods date. The results are also critically discussed in light of the North-South divide and the economic policy implications.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

(1) Background: Overall survival of the patients with renal cell carcinoma (RCC) depends mostly on extra-renal extension, documented by the invasion of the pelvicalyceal system, or the perinephric/renal sinus fat or the renal vein/its segmental intraparenchymal branches. Staging may be challenging because of the high inter-observer variability. We have introduced a more accurate procedure to detect the extra-renal extension and, to possibly evaluate the impact of such more laborious approach, we have compared the RCC pathological staging obtained following both standard and modified procedures; (2) Methods: We selected 54 consecutive cases of RCC diagnosed 18 months before and 54 consecutive cases diagnosed 18 months after the introduction of the new method of sampling. Clinico-pathological characteristics have been statistically analyzed; (3) Results: Most of the features analyzed were non statistically significative, except the extra-renal invasion. More precisely, the occurrence of retrograde venous invasion was higher in the cases grossly approached with the more accurate method; (4) Conclusions: Extra-renal extension to intraparenchymal renal vein branches may be underestimated, leading to an inappropriate under-staging. Using more accurate staging procedures, to disclose the occurrence of intra-renal veins tumoral thrombosis, helps to better define the pathological stage, allowing patients to benefit of better fitting treatments.

The reliable online analysis of volatile compounds in exhaled breath remains a challenge as a plethora of molecules occur in different concentration ranges (i.e. ppt to %), and need to be detected against an extremely complex background matrix. While this complexity is commonly addressed by hyphenating a specific analytical technique with appropriate preconcentration and/or preseparation strategies prior to detection, we herein propose the combination of three analytical tools based on truly orthogonal measurement principles as an alternative solution: field-asymmetric ion mobility spectrometry (FAIMS), Fourier-transform infrared (FTIR) spectroscopy-based sensors utilizing substrate-integrated hollow waveguides (iHWG), and luminescence sensing (LS). These three tools have been integrated into a single compact analytical platform suitable for online exhaled breath analysis. The analytical performance of this prototype system was tested via artificial breath samples containing nitrogen (N2), oxygen (O2), carbon dioxide (CO2) and acetone as a model volatile organic compound (VOC) commonly present and detected in breath. Functionality of the combined system was demonstrated by detecting these analytes in their respectively breath-relevant concentration range and mutually independent of each other generating orthogonal yet correlated analytical signals. Finally, adaptation of the system towards the analysis of real breath samples during future studies is discussed.

Forest fires are part of a set of natural disasters that have always affected regions of the world typically characterized by a tropical climate with long periods of drought. However, due to climate change in recent years, other regions of our planet have also been affected by this phenomenon, never seen before. One of them is certainly the Italian peninsula, and especially the regions of southern Italy. For this reason, the scientific community, as well as remote sensing one, is highly concerned in developing reliable techniques to provide useful support to the competent authorities. In particular, three specific tasks have been carried out in this work: (i) fire risk prevention, (ii) active fire detection, and (iii) post-fire area assessment. To accomplish these analyses, the capability of a set of spectral indices, derived from spaceborne remote sensing (RS) data, is assessed to monitor the forest fires. The spectral indices are obtained from Sentinel-2 multispectral images of the European Space Agency (ESA), which are free of charge and openly accessible. Moreover, the twin Sentinel-2 sensors allow to overcome some restrictions on time delivery and observation repeat time. The performance of the proposed analyses were assessed experimentally to monitor the forest fires occurred in two specific study areas during the summer of 2017: the volcano Vesuvius, near Naples, and the Lattari mountains, near Sorrento (both in Campania, Italy).

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension, which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary hypertension related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, hypertension per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, such as thiazide diuretics predisposing to skin cancer. As a result, under the light of the similar risk factors and overlapping pathophysiological mechanisms between hypertension and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Most head and neck cancers are diagnosed in advanced stages, when the curative interventions are no longer possible. The assessment and the multidisciplinary therapeutic approach of the locally advanced cases are difficult since the onset of the disease becomes a significant challenge for the whole attending team (including both the patient and his family) because they have to deal with to an extensive symptomatology (abundant secretions, refractory pain, mutilations predominantly in the cephalic area), with the cure of stomas (tracheostomy, gastrostomy) and with various post-therapeutic sequelae. The present paper reflects the impact of late diagnosis, the complexity of the multimodal specific oncological treatment (chemotherapy, radiotherapy, immunotherapy, pal-liative and terminal treatment), the adaptation of medical care to the psycho-emotional structure, having as an example the case of 54-year old patient (with his consent) diagnosed with pharyn-golaryngeal neoplasm who presented himself to “St. Luca” Chronic Disease Hospital, the Oncol-ogy-Palliative Care Department, in September 2021. In patients with locally advanced head and neck cancers, besides the specifically oncological therapeutic decisions, the empathic-emotional connection between the medical team with the patient and his family plays a key role in the ther-apeutic conduct.

This work deals with a systematic review of literature data concerning the theme of the integrated approach to occupational health and safety management, with particular reference to the programming of assistance plans, which guide the company's organizational choices also by aiming at the principles of the Total Worker Health. In the current regulatory framework on this issue, the UNI ISO 45001: 2018 standard assumes particular relevance, which defines the dynamic approach to occupational health and safety management systems, paying particular attention to external contextual factors that may influence corporate organizational decisions. The adoption of these systems is not mandatory, but allows companies to fulfill their duties in terms of health and safety at work, through an organizational approach aimed at awareness, involvement and participation of all subjects of the company prevention system, overcoming the phase of the mere technological and prescriptive approach, towards a holistic vision of prevention, which places the person at the center of preventive actions. In this context, the role of institutional networks and socio-economic partnerships assumes particular importance, in the activation of territorial assistance interventions to support companies for the improvement of risk management levels. To this end, the importance of verifying the effectiveness of assistance interventions emerges from the scientific debate, through the use of indicators such as quantitative ones for measuring the performance of all phases of the intervention with particular attention to the effects in terms of improved solutions developed.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

Superior mesenteric artery (SMA) syndrome or Wilkie’s syndrome is a vascular compression disorder that causes abnormal compression of the third portion of the duodenum by the SMA. It has a low incidence rate, higher in young women, and is rarely associated with the Nutcracker phenomenon: a condition of compression of the left renal vein between the SMA and the aorta, which manifests as pain in the left flank and pelvis. Here we report the case of a 54-year-old woman with a history of repeated episodes of abdominal pain caused by the Nutcracker syndrome and Wilkie's syndrome.

Previous reviews have investigated machine learning (ML) models used to predict the risk of developing preeclampsia but have not described how the ML models are intended to be deployed throughout pregnancy or feature performance. The aim of this study is to provide an overview of the existing ML models and their intended deployment patterns and performance along with identified features of high importance. This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed, Engineering Village, and the Association for Computing Machinery were searched between January and February 2024. A total of 86 studies were found of which 14 were included. Out of 12 studies, eight showed the intent to use the ML model as a single-use, two intended a dual-use, and two intended multiple-use. A total of seven studies listed the features of the highest importance. Systolic and diastolic blood pressure were listed along with mean arterial pressure to be of high importance. Out of four studies intending to use the ML model more than a single-use, three of them were conducted in the years 2023 and 2024, whereas the remaining study is from 2011. No ML model emerged as superior across the subgroups of PE. Utilizing body mass index and either mean arterial pressure or diastolic blood pressure and systolic blood pressure may benefit the performance. The deployment patterns are mainly single use being within the gestation weeks 11+0 to 14+1.

This paper provides an exhaustive narrative review of third-generation antipsychotics (TGAs), focusing on aripiprazole, cariprazine, brexpiprazole, and lurasidone for managing substance-induced psychosis. It includes a comprehensive literature review to evaluate the efficacy and tolerability of these medications. The paper emphasizes the distinct challenges in treating substance-induced psychosis, which is a psychiatric condition triggered by the misuse or withdrawal of various substances, leading to symptoms like hallucinations and delusions, and is distinct from primary psychotic disorders. It underscores the potential of TGAs in addressing both psychotic symptoms and substance-related issues, while highlighting the need for more research on long-term effects and advocating for an integrated approach combining pharmacological and psychological interventions